Serum Albumin Exhibits Nonlinear Relationship with Diabetic Retinopathy

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A secondary analysis of cross-sectional data found that serum albumin levels negatively correlated with the prevalence of diabetic retinopathy.

A new analysis identified a non-linear, negative association between serum albumin levels and the prevalence of diabetic retinopathy (DR) among patients with type 2 diabetes (T2D).1

Within the non-linear relationship, the investigative team based in China found the saturation point close to normal levels after fully adjusting for covariates. This may suggest the need for close attention to serum albumin levels among those with T2D.

“It is suggested that we should carefully monitor serum albumin levels and take appropriate intervention if necessary in patients with T2D in clinical practice,” wrote the investigative team led by Li Cai, department of ophthalmology at Shenzhen University General Hospital.

Previously reported evidence identified a significant negative correlation between serum albumin levels and the prevalence of DR.2 These data suggested that increased oxidative stress and inflammatory response due to low serum albumin could be the primary cause of DR progression.

However, according to Cai and colleagues, most of these trials concluded on this relationship based on linear analysis.1 In contrast, the relationship between exposure and outcomes is often non-linear in clinical research.

Thus, the investigative team conducted a secondary analysis of existing trial data to validate the potential non-linear association between serum albumin and DR. The analysis involved data from a retrospective, cross-sectional study of 426 patients with T2D hospitalized in the Guangdong Provincial People’s Hospital from December 2017 to November 2018. All relevant clinical information was collected from the electronic medical record.

For the analysis, based on international grading criteria, DR was classified as no retinopathy, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR, and proliferative DR (PDR). Cai and colleagues conducted a two-piecewise logistics regression model to assess the non-linear relationship between serum albumin levels and the prevalence of DR. To evaluate a threshold or saturation effect, the inflection point was measured using a maximum likelihood ratio and a recursive algorithm.

The study population consisted of 240 male and 186 female patients, with a mean age of 59 years and a mean diabetes duration of 10 years. Among the population, 167 patients were diagnosed with DR, with a prevalence of approximately 39%. Those with DR had a higher proportion of female patients, a longer duration of diabetes, and a lower body mass index.

Upon analysis, in the fully adjusted model, the prevalence of DR decreased by approximately 8% for each additional 1 g/L of serum albumin (odds ratio [OR], 0.89; 95% CI, 0.85 to 1.00; P = .0474). In sensitivity analysis, investigators noted the trend of increase was not significant in the fully adjusted model (P = .0742), suggesting the relationship between serum albumin and the prevalence of DR was nonlinear.

The team calculated the inflection point as 38.10 g/L in the fully adjusted two-piecewise logistics regression model. Analyses showed serum albumin was negatively associated with the prevalence of DR when it was <38.10 g/L (OR, 0.82; 95% CI, 0.72 - 0.94; P = .0037). On the other hand, the association between serum albumin and DR was no longer significant when the levels were >38.10 g/L (OR, 1.12; 95% CI, 0.92 - 1.35; P = .2637).

Cai and colleagues recommended raising serum albumin levels to a minimum of 38.10 g/L to diminish the risk of DR. The team noted the analysis tested the association rather than causation, making prospective studies crucial to confirm these findings.

“Further prospective research is needed to determine whether the change in serum albumin levels affected the incidence of DR,” Cai and colleagues wrote.


  1. Zeng, GQ., Yao, YF., Zhong, JB. et al. The non-linear relationship between serum albumin and diabetic retinopathy in type 2 diabetes mellitus: a secondary analysis based on a cross-sectional study. BMC Ophthalmol 24, 94 (2024).
  2. Wang GX, Fang ZB, Li JT, Huang BL, Liu DL, Chu SF, Li HL. The correlation between serum albumin and diabetic retinopathy among people with type 2 diabetes mellitus: NHANES 2011-2020. PLoS One. 2022 Jun 16;17(6):e0270019. doi: 10.1371/journal.pone.0270019. PMID: 35709212; PMCID: PMC9202838.